IT1272179B - METHODOLOGY TO REPRODUCE IN VITRO THE PROTEOLITHIC ACTIVITY OF THE NS3 PROTEASE OF THE VIRUS HCV. - Google Patents
METHODOLOGY TO REPRODUCE IN VITRO THE PROTEOLITHIC ACTIVITY OF THE NS3 PROTEASE OF THE VIRUS HCV.Info
- Publication number
- IT1272179B IT1272179B ITRM940092A ITRM940092A IT1272179B IT 1272179 B IT1272179 B IT 1272179B IT RM940092 A ITRM940092 A IT RM940092A IT RM940092 A ITRM940092 A IT RM940092A IT 1272179 B IT1272179 B IT 1272179B
- Authority
- IT
- Italy
- Prior art keywords
- ns4a
- methodology
- precursor
- protease
- hcv
- Prior art date
Links
- 230000000694 effects Effects 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 4
- 238000000338 in vitro Methods 0.000 title abstract 3
- 108091005804 Peptidases Proteins 0.000 title 1
- 239000004365 Protease Substances 0.000 title 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title 1
- 241000700605 Viruses Species 0.000 title 1
- 101800001020 Non-structural protein 4A Proteins 0.000 abstract 8
- 239000002243 precursor Substances 0.000 abstract 4
- 102000012479 Serine Proteases Human genes 0.000 abstract 3
- 108010022999 Serine Proteases Proteins 0.000 abstract 3
- 230000002255 enzymatic effect Effects 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 abstract 1
- 230000004913 activation Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000007824 enzymatic assay Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 239000013600 plasmid vector Substances 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 230000002797 proteolythic effect Effects 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
- G01N33/5767—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis non-A, non-B hepatitis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
- C12N2770/00011—Details
- C12N2770/24011—Flaviviridae
- C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
- C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Organic Chemistry (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Si tratta di una metodologia, per riprodurre in vitro l'attività di serino - proteasi associata alla proteina NS3 di HCV, che comprende l'utilizzo sia di sequenze contenute in NS3 che di sequenze contenute in NS4A. Questa metodologia sfrutta la capacità della proteina di HCV NS4A, o di sequenze in essa contenute, di agire come cofattore della attività serino - proteasica o più in generale di attività enzimatiche associate a NS3. L'attività ottimale di serino - proteasi si ottiene quando NS4A è presente in un rapporto molare di almeno 1:1 con NS3. NS3 ed NS4A possono essere anche incorporati nella miscela di reazione come precursore NS3-NS4A, in quanto questo precursore genererà, mediante un evento autoproteolitico, quantità equimolari di NS3 ed NS4A. E' anche possibile mutare il sito di taglio tra NS3 ed NS4A in un precursore, in modo che NS4A rimanga covalentemente legato a NS3. Da tale precursore non proteolizzabile possono essere successivamente rimosse le sequenze che non influenzano l'attività proteolitica di NS3.L'invenzione si riferisce anche ad una composizione di materia che comprende sequenze contenute in NS3 ed NS4A, e all'uso di queste composizioni per la messa a punto di un saggio enzimatico capace di selezionare, a fini terapeutici, composti inibitori dell'attività enzimatica associata a NS3.La figura rappresenta vettori plasmidici utilizzati nella metodologia per l'attivazione della proteasi NS3 di HCV in cellule in coltura e in vitro.This is a methodology for reproducing in vitro the serine - protease activity associated with the NSV protein of HCV, which includes the use of both sequences contained in NS3 and sequences contained in NS4A. This methodology exploits the ability of the HCV protein NS4A, or of sequences contained in it, to act as a cofactor of the serine-protease activity or more generally of enzymatic activities associated with NS3. The optimal serine - protease activity is obtained when NS4A is present in a molar ratio of at least 1: 1 with NS3. NS3 and NS4A can also be incorporated into the reaction mixture as a NS3-NS4A precursor, since this precursor will generate, by means of a self-protective event, equimolar quantities of NS3 and NS4A. It is also possible to change the shear site between NS3 and NS4A into a precursor, so that NS4A remains covalently bound to NS3. The sequences that do not influence the proteolytic activity of NS3 can be subsequently removed from this non-proteolyzable precursor. The invention also refers to a composition of matter which includes sequences contained in NS3 and NS4A, and to the use of these compositions for the development of an enzymatic assay capable of selecting, for therapeutic purposes, inhibitory compounds of the enzymatic activity associated with NS3.The figure represents plasmid vectors used in the methodology for the activation of the NS3 protease of HCV in cultured and in vitro cells.
Priority Applications (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITRM940092A IT1272179B (en) | 1994-02-23 | 1994-02-23 | METHODOLOGY TO REPRODUCE IN VITRO THE PROTEOLITHIC ACTIVITY OF THE NS3 PROTEASE OF THE VIRUS HCV. |
US08/700,356 US5739002A (en) | 1994-02-23 | 1995-02-14 | Method for reproducing in vitro the Proteolytic activity of the NS3 protease of hepatitis C virus (HCV) |
JP52223995A JP3280384B2 (en) | 1994-02-23 | 1995-02-14 | Method for in vitro regeneration of proteolytic activity of NS3 protease of hepatitis C virus (HCV) |
PCT/IT1995/000018 WO1995022985A1 (en) | 1994-02-23 | 1995-02-14 | Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv) |
BR9506931A BR9506931A (en) | 1994-02-23 | 1995-02-14 | Process to reproduce in vitro the proteolytic activity of the ns3 protease from hcv composition of matter and use thereof |
DK95909937T DK0746333T3 (en) | 1994-02-23 | 1995-02-14 | Method for in vitro reproduction of the proteolytic activity of the hepatitis C virus (HCV) NS3 protease |
AU18223/95A AU691259B2 (en) | 1994-02-23 | 1995-02-14 | Method for reproducing in vitro the proteolytic activity of the NS3 protease of hepatitis C virus (HCV) |
AT95909937T ATE179611T1 (en) | 1994-02-23 | 1995-02-14 | METHOD FOR PRODUCING THE PROTEOLYTIC EFFECT OF NS3 HEPATITIS C VIRUS (HCV) IN VITRO |
RU96119350A RU2149185C1 (en) | 1994-02-23 | 1995-02-14 | Method of in vitro reproduction of proteolytic activity of hepatitis c virus protease ns3 |
ES95909937T ES2132644T3 (en) | 1994-02-23 | 1995-02-14 | METHOD FOR IN VITRO REPRODUCING PROTEOLYTIC ACTIVITY OF HEPATITIS C (HCV) VIRUS PROTEASE NS3. |
EP95909937A EP0746333B1 (en) | 1994-02-23 | 1995-02-14 | Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv) |
CA002182521A CA2182521C (en) | 1994-02-23 | 1995-02-14 | Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv) |
DE69509504T DE69509504T2 (en) | 1994-02-23 | 1995-02-14 | METHOD FOR PRODUCING THE PROTEOLYTIC EFFECT OF NS3 HEPATITIS C VIRUS (HCV) IN VITRO |
HK98111982A HK1010988A1 (en) | 1994-02-23 | 1998-11-13 | Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv) |
GR990401236T GR3030166T3 (en) | 1994-02-23 | 1999-05-07 | Method for reproducing in vitro the proteolytic activity of the ns3 protease of hepatitis c virus (hcv) |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITRM940092A IT1272179B (en) | 1994-02-23 | 1994-02-23 | METHODOLOGY TO REPRODUCE IN VITRO THE PROTEOLITHIC ACTIVITY OF THE NS3 PROTEASE OF THE VIRUS HCV. |
Publications (3)
Publication Number | Publication Date |
---|---|
ITRM940092A0 ITRM940092A0 (en) | 1994-02-23 |
ITRM940092A1 ITRM940092A1 (en) | 1995-08-23 |
IT1272179B true IT1272179B (en) | 1997-06-16 |
Family
ID=11402272
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ITRM940092A IT1272179B (en) | 1994-02-23 | 1994-02-23 | METHODOLOGY TO REPRODUCE IN VITRO THE PROTEOLITHIC ACTIVITY OF THE NS3 PROTEASE OF THE VIRUS HCV. |
Country Status (15)
Country | Link |
---|---|
US (1) | US5739002A (en) |
EP (1) | EP0746333B1 (en) |
JP (1) | JP3280384B2 (en) |
AT (1) | ATE179611T1 (en) |
AU (1) | AU691259B2 (en) |
BR (1) | BR9506931A (en) |
CA (1) | CA2182521C (en) |
DE (1) | DE69509504T2 (en) |
DK (1) | DK0746333T3 (en) |
ES (1) | ES2132644T3 (en) |
GR (1) | GR3030166T3 (en) |
HK (1) | HK1010988A1 (en) |
IT (1) | IT1272179B (en) |
RU (1) | RU2149185C1 (en) |
WO (1) | WO1995022985A1 (en) |
Families Citing this family (50)
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US5843752A (en) * | 1995-05-12 | 1998-12-01 | Schering Corporation | Soluble active hepatitis C virus protease |
US5767233A (en) * | 1995-05-12 | 1998-06-16 | Schering Corporation | Soluble cleavable substrates of the hepatitis C virus protease |
IT1278077B1 (en) * | 1995-05-25 | 1997-11-17 | Angeletti P Ist Richerche Bio | METHODOLOGY TO REPRODUCE IN VITRO THE ACTIVITIES OF RNA-DEPENDENT RNA POLYMERASE AND OF TERMINAL NUCLEOTIDYLTRANSPHERASE CODED BY THE |
US5990276A (en) * | 1996-05-10 | 1999-11-23 | Schering Corporation | Synthetic inhibitors of hepatitis C virus NS3 protease |
AU2933797A (en) * | 1996-05-10 | 1997-12-05 | Schering Corporation | Synthetic inhibitors of hepatitis c virus ns3 protease |
US6153579A (en) * | 1996-09-12 | 2000-11-28 | Vertex Pharmaceuticals, Incorporated | Crystallizable compositions comprising a hepatitis C virus NS3 protease domain/NS4A complex |
EP1364961B1 (en) * | 1996-09-12 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Crystallizable compositions comprising a hepatitis c virus ns3 protease domain/ns4a complex and crystals thereby obtained |
US5861297A (en) * | 1996-09-27 | 1999-01-19 | Merck & Co., Inc. | Detergent-free hepatitis C protease |
US6436666B1 (en) | 1996-10-17 | 2002-08-20 | Chiron Corporation | Protease regulator screening assay |
WO1998037180A2 (en) * | 1997-02-22 | 1998-08-27 | Abbott Laboratories | Hcv fusion protease and polynucleotide encoding same |
US6251583B1 (en) | 1998-04-27 | 2001-06-26 | Schering Corporation | Peptide substrates for HCV NS3 protease assays |
US6280940B1 (en) | 1998-08-05 | 2001-08-28 | Agouron Pharmaceuticals, Inc. | Reporter gene system for use in cell-based assessment of inhibitors of the Hepatitis C virus protease |
US6323180B1 (en) | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
JP2002534084A (en) | 1999-01-08 | 2002-10-15 | ブリストル−マイヤーズ スクイブ カンパニー | Modified form of hepatitis C virus NS3 protease |
AU5788800A (en) * | 1999-07-07 | 2001-01-22 | Du Pont Pharmaceuticals Company | Peptide boronic acid inhibitors of hepatitis c virus protease |
WO2001038538A1 (en) * | 1999-11-23 | 2001-05-31 | Viropharma Incorporated | Polymerase compositions and methods of use thereof |
MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
PL206255B1 (en) * | 2000-07-21 | 2010-07-30 | Dendreon Corporationdendreon Corporation | Novel peptides as ns3-serine protease inhibitors of hepatitis c virus |
US7244721B2 (en) * | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
BR0112666A (en) * | 2000-07-21 | 2003-06-10 | Schering Corp | Peptides as inhibitors of hepatitis C virus ns3-serine protease |
AR029851A1 (en) * | 2000-07-21 | 2003-07-16 | Dendreon Corp | NEW PEPTIDES AS INHIBITORS OF NS3-SERINA PROTEASA DEL VIRUS DE HEPATITIS C |
US7022830B2 (en) | 2000-08-17 | 2006-04-04 | Tripep Ab | Hepatitis C virus codon optimized non-structural NS3/4A fusion gene |
JP4299540B2 (en) * | 2001-01-23 | 2009-07-22 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | Hepatitis C virus replicon and replicon enhanced cells |
JP2005504087A (en) * | 2001-09-28 | 2005-02-10 | イデニクス(ケイマン)リミテツド | Methods and compositions for the treatment of hepatitis C virus using 4 'modified nucleosides |
EP2172552A3 (en) | 2001-10-11 | 2010-07-21 | Merck Sharp & Dohme Corp. | Recombinant nucleic acids comprising regions of AD6 |
AU2002337840B2 (en) | 2001-10-11 | 2007-08-09 | Msd Italia S.R.L. | Hepatitis C virus vaccine |
ATE426682T1 (en) * | 2002-04-16 | 2009-04-15 | Merck & Co Inc | HEPATITIS C VIRUS TEST SYSTEMS |
DE602004024658D1 (en) * | 2003-02-13 | 2010-01-28 | Merck & Co Inc | METHOD FOR TRANSFERRING CELL CULTURAL REPLICATION ACTIVITY TO DIFFERENT HEPATITIS C VIRUS ISOLATES |
WO2006121468A1 (en) * | 2004-11-22 | 2006-11-16 | Genelabs Technologies, Inc. | 5-nitro-nucleoside compounds for treating viral infections |
WO2006093987A1 (en) * | 2005-02-28 | 2006-09-08 | Genelabs Technologies, Inc. | Tricyclic-nucleoside compounds for treating viral infections |
US7834145B2 (en) * | 2005-03-22 | 2010-11-16 | Merck Sharp & Dohme Corp. | HCV protease substrates |
WO2006116557A1 (en) * | 2005-04-25 | 2006-11-02 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
AU2006261132A1 (en) * | 2005-06-24 | 2006-12-28 | Genelabs Technologies, Inc. | Heteroaryl derivatives for treating viruses |
CA2627247C (en) * | 2005-10-28 | 2013-04-02 | Boehringer Ingelheim International Gmbh | Hepatitis c virus ns2/3 activity assay |
US20090203008A1 (en) | 2006-06-08 | 2009-08-13 | Ludmerer Steven W | Rapid method to determine inhibitor sensitivity of NS3/4A protease sequences cloned from clinical samples |
KR20090029827A (en) * | 2006-07-20 | 2009-03-23 | 제네랩스 테크놀로지스, 인코포레이티드 | Polycyclic viral inhibitors |
US20100216161A1 (en) | 2009-02-26 | 2010-08-26 | Vertex Pharmaceuticals Incorporated | Method for identifying protease inhibitors |
EP2481807A3 (en) | 2007-03-09 | 2013-04-03 | Merck Sharp & Dohme Corp. | In vivo HCV resistance to anti-viral inhibitors |
WO2009022236A2 (en) | 2007-08-16 | 2009-02-19 | Tripep Ab | Immunogen platform |
WO2009029729A1 (en) * | 2007-08-31 | 2009-03-05 | Genelabs Technologies, Inc. | Amino tricyclic-nucleoside compounds, compositions, and methods of use |
US8324239B2 (en) | 2010-04-21 | 2012-12-04 | Novartis Ag | Furopyridine compounds and uses thereof |
MA34462B1 (en) | 2010-07-22 | 2013-08-01 | Novartis Ag | 2,3,5-TRISUBSTITUTED THIOPHENE COMPOUNDS AND USES THEREOF |
US9351989B2 (en) | 2010-12-29 | 2016-05-31 | Inhibitex, Inc. | Substituted purine nucleosides, phosphoroamidate and phosphorodiamidate derivatives for treatment of viral infections |
WO2014139587A1 (en) | 2013-03-15 | 2014-09-18 | Okairòs Ag | Improved poxviral vaccines |
WO2017025782A1 (en) | 2014-09-17 | 2017-02-16 | Glaxosmithkline Biologicals Sa | Improved poxviral vaccines |
US11965191B2 (en) | 2018-01-18 | 2024-04-23 | California Institute Of Technology | Programmable protein circuits in living cells |
WO2019147478A2 (en) | 2018-01-18 | 2019-08-01 | California Institute Of Technology | Programmable protein circuits in living cells |
US11453893B2 (en) | 2018-08-30 | 2022-09-27 | California Institute Of Technology | RNA-based delivery systems with levels of control |
US11542305B2 (en) | 2018-08-31 | 2023-01-03 | California Institute Of Technology | Synthetic protein circuits detecting signal transducer activity |
US11667676B2 (en) | 2019-01-10 | 2023-06-06 | California Institute Of Technology | Synthetic system for tunable thresholding of protein signals |
-
1994
- 1994-02-23 IT ITRM940092A patent/IT1272179B/en active IP Right Grant
-
1995
- 1995-02-14 RU RU96119350A patent/RU2149185C1/en active
- 1995-02-14 DE DE69509504T patent/DE69509504T2/en not_active Expired - Lifetime
- 1995-02-14 JP JP52223995A patent/JP3280384B2/en not_active Expired - Fee Related
- 1995-02-14 DK DK95909937T patent/DK0746333T3/en active
- 1995-02-14 EP EP95909937A patent/EP0746333B1/en not_active Expired - Lifetime
- 1995-02-14 AT AT95909937T patent/ATE179611T1/en active
- 1995-02-14 CA CA002182521A patent/CA2182521C/en not_active Expired - Fee Related
- 1995-02-14 US US08/700,356 patent/US5739002A/en not_active Expired - Lifetime
- 1995-02-14 AU AU18223/95A patent/AU691259B2/en not_active Ceased
- 1995-02-14 ES ES95909937T patent/ES2132644T3/en not_active Expired - Lifetime
- 1995-02-14 BR BR9506931A patent/BR9506931A/en not_active Application Discontinuation
- 1995-02-14 WO PCT/IT1995/000018 patent/WO1995022985A1/en active IP Right Grant
-
1998
- 1998-11-13 HK HK98111982A patent/HK1010988A1/en not_active IP Right Cessation
-
1999
- 1999-05-07 GR GR990401236T patent/GR3030166T3/en unknown
Also Published As
Publication number | Publication date |
---|---|
WO1995022985A1 (en) | 1995-08-31 |
JP3280384B2 (en) | 2002-05-13 |
EP0746333A1 (en) | 1996-12-11 |
DE69509504T2 (en) | 1999-09-02 |
DE69509504D1 (en) | 1999-06-10 |
EP0746333B1 (en) | 1999-05-06 |
US5739002A (en) | 1998-04-14 |
JPH10500005A (en) | 1998-01-06 |
RU2149185C1 (en) | 2000-05-20 |
HK1010988A1 (en) | 1999-07-02 |
GR3030166T3 (en) | 1999-08-31 |
ATE179611T1 (en) | 1999-05-15 |
CA2182521C (en) | 1999-07-06 |
ITRM940092A0 (en) | 1994-02-23 |
BR9506931A (en) | 1997-09-09 |
ES2132644T3 (en) | 1999-08-16 |
CA2182521A1 (en) | 1995-08-31 |
AU691259B2 (en) | 1998-05-14 |
ITRM940092A1 (en) | 1995-08-23 |
DK0746333T3 (en) | 1999-11-01 |
AU1822395A (en) | 1995-09-11 |
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